[Mechanism of anti-inflammatory action of 2-(2-fluoro-4-biphenylyl) propionic acid (flurbiprofen)]. 1976

S Masumoto, and C Masuda

Anti-inflammatory mechanism of 2-(2-fluoro-4-biphenylyl) propionic acid (Flurbiprofen, FP-70) was studied by various analysis in comparison with other drugs. It was found in the test of rat edema induced by various phlogists that carrageenin and yeast-induced edemas were markedly inhibited by FP-70, whereas dextran, formalin, serotonin and bradykinin-induced edemas were scarcely inhibited by FP-70. The action of FP-70 was similar to that of soy bean trypsin inhibitor. However, FP-70 showed no effects on kinin synthetase and kininase. FP-70 showed a marked inhibition on prostaglandin synthesis. The inhibitory effect of FP-70 was 10.1, 96.5 and 2280.6 times as large as indomethacin, ibuprofen and acetylsalicylic acid, respectively. FP-70 did not inhibit the permeability of dye induced by prostaglandin E2 in the rat skin. FP-70 inhibited the acid phosphatase and beta-glucuronidase activities of isolated lysosome of rat liver and also suppressed the release of acid phosphatase from the lysosome. These effects were similar to those of indomethacin. On the other hand, FP-70 suppressed markedly the heat-induced hemolysis of dog erythrocytes. The effect was similar to that of indomethacin and was 10 times stronger than those of ibuprofen, ibufenac and phenylbutazone. Activation of rat liver mitochondrial ATPase by FP-70 at a concentration of 10 muM was 74.7%, while indomethacin showed 37.8% activation at the same concentration. FP-70 as well as ibuprofen and phenylbutazone uncoupled the oxidative phosphorylation in rat liver mitochondria. From the above and previously reported results, it is suggested that the potent anti-inflammatory action of FP-70 is the result of the following effects; inhibition on the protein and leucocyte migration, inhibition on the prostaglandin synthesis, stabilization of the cell membrane and activation of ATPase.

UI MeSH Term Description Entries
D007703 Peptidyl-Dipeptidase A A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of ANGIOTENSIN I to ANGIOTENSIN II, with increase in vasoconstrictor activity, but no action on angiotensin II. It is also able to inactivate BRADYKININ, a potent vasodilator; and has a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. (From https://www.uniprot.org April 15, 2020). ACE1 Angiotensin-Converting Enzyme 1,ACE1 Protein,Angiotensin Converting Enzyme,Angiotensin Converting Enzyme 1,Antigens, CD143,CD143 Antigens,Dipeptidyl Carboxypeptidase I,Kininase II,Peptidase P,Angiotensin I-Converting Enzyme,Carboxycathepsin,Dipeptidyl Peptidase A,Kininase A,ACE1 Angiotensin Converting Enzyme 1,Angiotensin I Converting Enzyme,Carboxypeptidase I, Dipeptidyl,Peptidyl Dipeptidase A
D007705 Kinins A generic term used to describe a group of polypeptides with related chemical structures and pharmacological properties that are widely distributed in nature. These peptides are AUTACOIDS that act locally to produce pain, vasodilatation, increased vascular permeability, and the synthesis of prostaglandins. Thus, they comprise a subset of the large number of mediators that contribute to the inflammatory response. (From Goodman and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, p588) Kinin
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D008297 Male Males
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D011422 Propionates Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure. Propanoate,Propanoic Acid,Propionate,Propanoates,Propanoic Acid Derivatives,Propanoic Acids,Propionic Acid Derivatives,Propionic Acids,Acid, Propanoic,Acids, Propanoic,Acids, Propionic,Derivatives, Propanoic Acid,Derivatives, Propionic Acid
D011453 Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Prostaglandin,Prostanoid,Prostanoids
D011458 Prostaglandins E (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities. PGE
D002199 Capillary Permeability The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement. Microvascular Permeability,Permeability, Capillary,Permeability, Microvascular,Vascular Permeability,Capillary Permeabilities,Microvascular Permeabilities,Permeabilities, Capillary,Permeabilities, Microvascular,Permeabilities, Vascular,Permeability, Vascular,Vascular Permeabilities
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog

Related Publications

S Masumoto, and C Masuda
September 1975, Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
S Masumoto, and C Masuda
January 1980, Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
S Masumoto, and C Masuda
April 1974, Journal of pharmaceutical sciences,
S Masumoto, and C Masuda
May 1977, Il Farmaco; edizione scientifica,
Copied contents to your clipboard!